Ketamine and natural remedies for chronic depression

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Ketamine can teach us a lot about natural remedies for depression, said Peter Bongiorno, ND, LAc, co-medical director of Inner Source Health, at the 2020 Integrative Healthcare Symposium in New York City.

Historically, ketamine has been used as a hallucinogen and clinical anesthetic. In the 1990s, it became used in sub-anesthetic doses for psychomimetic and dissociative effects.

Since then, ketamine has become very popular, Bongiorno said.  He said he does use it in his office, and he says, “it’s more of a process than just exposing receptors to a drug.”

In 2006, a randomized trial found that 71 percent of depression symptoms improved within one day and 29 percent were symptom-free in a day. More recently, in 2017, Yale University School of Medicine treated 14 suicidal patients in the emergency room with single subanesthetic intravenous bolus of ketamine and suicidal ideation was resolved within 40 minutes.  

Structurally, ketamine has two isomers, S-ketamine and R-ketamine. S-ketamine is anesthetic and R-ketamine is hallucinogenic, Bongiorno said. Ketamine is a N-methyl-D-aspartate (NMDA) receptor antagonist. It increases mammalian specific target of rapamycin, sustained activation of α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid receptor (AMPAR), binds to acetylcholine’s nicotinic receptors, binds to sigma receptors, activates brain-derived neurotrophic factor (BDNF), and opioid activation. Ketamine is a glutamate blocker, Bongiorno said.

Functionally, ketamine effects include dendritic remodeling, it builds synaptic spines, calms cortical input, inhibit the thalamus, and potentiates effects of gamma-aminobutyric acid.

As promising as ketamine is, Bongiorno said there are some drawbacks. There is lack of data to ensure efficacy, effects are short-lived, and there are several side effects. It’s meant to be used as in a dissociative dose, he said.

Bongiorno suggests natural treatment considerations that can mimic the mechanisms of ketamine for chronic depression symptoms. His recommendations include:

  • Sleep
  • Water
  • Exercise
  • Nutrition
  • Supplements

Contrary to popular recommendations, Bongiorno said sleep deprivation can offer relief for 40 percent to 60 percent of patients with depression, effecting GABA and glutamate contents in the brain. Unfortunately, once even a small amount of sleep thereafter sems to initiate the depression, but it is something to think about, Bongiorno said.  

Water is naturally glutamate lowering and raises cerebral water concentrations. Exercise balances mTOR in the brain and activates mTORC1, he said.

When it comes to nutrition, Bongiorno said the first step is reducing sodium and avoiding glutamate-containing foods. Foods he says to recommend include peas, mushrooms, broccoli, tomatoes, matured cheese, and cured meats.

Supplements individually cannot produce the same results as ketamine, but when combined can modulate receptors and cell signaling mechanisms and affect individual parts of the cell in complex ways. Supplements Bongiorno recommends exploring include:

  • Omega-3 fatty acids
  • Riboflavin
  • Magnesium
  • Lithium
  • Glutathione
  • Curcumin
  • Berberines

A word of caution, Bonjiorno said practitioners should not give glycine to depressed patients. It may be excitatory in glutamine excess patients.

Neurosteroids binds to sigma receptors, including vitamin D, dehydroepiandrosterone, and pregnenolone. Bongiorno also recommends several herbs, including salvia divinorum, sorcosine, red cover and isoflavones, and Chinese herbal formulas like yueju.

“We can learn a lot from ketamine to inform natural treatments and get the patient on the right track,” said Bongiorno. “I’m really starting to think that this is the way to go.”